The long-term objective of these studies is to determine whether a unique set of CD8 T cells can play a role in cancer therapy using the immune system. Specifically, we and others found that CD8 (killer) T cells that secrete a chemical substance (cytokine) known as interleukin-17 (IL-17) appear to last longer and function better than those that secrete other cytokines. We plan to determine how these cells (called Tc17) kill tumors, and whether they absolutely need IL-17 to work. Next, we plan to figure out the best way to make these cells, focusing on whether the target they recognize (antigen) plays a major role in that process. Finally, we found that Tc17 cells show an extremely interesting property that might be important for their superior anti-tumor function: in animals these cells convert, or flip the cytokines they produce. This conversion process is fascinating, and a better understanding of it might be important in understanding how other tumor treatments that use the immune system work. These experiments will not be undertaken in a vacuum; several groups, including ours have already showed that CD8 T cells that make IL-17 have superior anti-tumor activity in animals. Thus, these studies are designed to follow up on those intriguing results in an effort to engineer and understand a superior method for cancer treatment. PUBLIC HEALTH RELEVANCE: This project is directly relevant to cancer treatment, a significant public health problem. Using an animal model, we will investigate a new method for cancer treatment that uses a patient's own immune cells to attack tumors; these cells will be removed from the body, manipulated in a novel way, and then returned. If our animal studies are successful, similar methods can be readily tested in humans.